The major structural proteins collagen and elastin will be examined in any person that clinically appears to have defective connective tissue. In particular emphasis will be placed on those persons with the heritable disorders of connective tissue, e.g. Ehlers-Danlos, osteogenesis imperfecta, Marfan syndrome, homocystinuria, cutis laxa, the various chondro- and osteodystrophies, pseudoxanthoma elasticum, and other poorly defined mesenchymal dysplasias. Since most of these patients are children, the large amounts of tissue necessary for traditional methodology rarely become available. Micro techniques have therefore been developed to comprehensively screen tissue samples for primary structure and the multiple post ribosomal enzymatic modifications that occur in these proteins. Moreover, since collagen is a major product of fibroblasts, the biosynthesis of collagen and followup of any observations derived from the micro methods can be performed in fibroblast tissue culture without further inconvenience to the patient. The following analyses for collagen can be performed on about 50 mgm of skin, an amount easily obtained by ellipse skin biopsy without significant morbidity to the patient: 1. Electron microscopy; 2. Solubility; 3. Quantitation of chain structure-relative amounts of polymers, pro alpha and beta chains, alpha and beta chains by gel electrophoresis; 4. Amino acid analysis including specific analyses for 3-hydroxyproline, 4-hydroxyproline, hydroxylysine, galactosylhydroxylysine, and glucosyl-galactosylhydroxylysine by modified amino acid analysis; 5. Cross-link analysis following sodium borotritide reduction; 6. Primary structure analysis following cyanogen bromide cleavage and disc gel electrophoresis (molecular sieve and ion exchange chromotography add to this information when additional tissue is available); 7. Biosynthesis of collagen and procollagen by fibroblast tissue culture. Similar methods can be used for other tissue samples e.g. bone, cartilage. Elastin will be studied in tissue samples following hot alkali extraction. Its amino acid analysis and content of unique amino acids lysinonorleucine and esmosine will be determined.